1. Field of the Invention
The invention relates to a range of new products; processes for preparing them from dry biological polymers (biopolymers) using ionizing radiation in the solid—non fluid state in the presence of an unsaturated gas under specified reaction conditions and the uses thereof.
2. The Prior Art
It is known in the art to subject certain types of polymeric materials to irradiation in order to achieve a number of different goals, although to our knowledge it is not known in the art to subject such biopolymers to high energy irradiation in the presence of a mediating gas, e.g., acetylene, in order to modify the biopolymer so as to enhance its properties in one or more respects. The following U.S. Pat. No. 3,215,634 (Walker); U.S. Pat. No. 4,024,073 (Shimizu); U.S. Pat. No. 4,716,224 (Sakurai); U.S. Pat. No. 4,746,514 (Warne); U.S. Pat. No. 4,987,222; (De Ambrosi); and U.S. Pat. No. 5,376,692 (Park); and published foreign application WO 96/03147; (Fidia, S.p.A) are of interest, but are not significantly relevant. For example, none of the art teaches irradiation of polymeric materials in the solid state, including Warne ('514) who does use an ethylenically unsaturated compound application WO 96/03147; (Fidia, S.p.A) are somewhat, but not significantly relevant, which is not a gas.
Sakurai ('224) teaches the cross-linking of hyaluronic acid with polyfunctional epoxy compounds under certain conditions, none of which teach the use of ionizing radiation/unsaturated [alkenic or alkynic] gases.
Walker ('634) and Shimizu ('073) also disclose the use of various chemical cross-linking agents for preparing cross-linked polysaccharide products.
De Ambrosi ('222) discloses the controlled preparation of low molecular weight glucosaminoglycans by depolymerizing high molecular weight glucosaminoglycans using γ radiation.
Warne ('514) teaches away from the invention. Warne discloses the preparation of cross-linked hydrogels by subjecting a polysaccharide, specifically, nothing of higher molecular weight than a pentasaccharide, to ionizing radiation in the presence of an ethylenically unsaturated compound (but not a gas) having at least one hydrophilic group.
Park ('692) discloses proteins, e.g., albumin, that are functionalized so that when the albumin is bonded to a blood compatible substrate, and after treatment with radiation, free radicals formed on both the protein and the substrate chemically bind to one another. This reference does not teach or suggest cross-linking the polymers by using ionizing radiation in the presence of an unsaturated gas which forms part of the cross-link.
Fidia (PCT application no. WO 96/03147) teaches the synthesis of chemical gels from polyelectrolyte polysaccharides, including HA and HA-benzyl ester by γ-irradiation, preceded by functionalizing to introduce olefinic bonds, into the structure thereof. The only functionalizing agent. disclosed is glycidyl acrylate. Other, less relevant foreign patents such as EP 000 038 426; JP 360,143,991; JP 363,301,234; JP 401,118,529; DE 004,123,889; DE 004,124,338; and JP 406,073,102 are noted.
Non-patent literature relating to the subject matter of this invention, particularly, certain studies conducted on some of the starting materials used herein and the effect of ionizing radiations on uncharged polysaccharides (such as starch and cellulose) and on polyelectrolyte polysaccharides (such as hyaluronic acid and its cross-linked derivative hylan, alginates, heparin etc) is to induce degradation, with main chain scission leading to a decrease in molecular weight and viscosity are discussed in:
The effect of sterilizing doses of γ-irradiation on the molecular weight and emulsification properties of gum arabic; Blake, et al, Food Hydrocolloids 1988, Vol.2 No.5, p.407-415; The effects of radiation on carbohydrates (Phillips, G., Chapter 26 pages 1217-1297 in “The Carbohydrates”, second edition. (Eds. Ward Pigman/Derek Horton), Academic Press Inc. New York, 1980); Free radical formation and degradation of cellulose by ionizing radiations. (Nakamura et al. Polymer Photochemistry, 1985, 6, 135-159); Photochemistry and radiation chemistry of cellulose (Phillips et al. Cellulose Chemistry and Its Applications 1985, 290-311); Radiation effects on the biological activity and molecular weight parameters of heparin. (Edwards et al. Carbohydrate Polymers, 1985, 5, 473-478); The radiation-induced degradation of hyaluronic acid. (Deeble et al. Radiat.Phys.Chem. 1991, Vol.37, No.1, 115-118); Susceptibility of Connective Tissue: Biomaterials to Radiation. (Phillips et al. Journal of Korea Biomaterial Research Institute, Vol. 1, No. 1, August 1991, p.92); The enhanced stability of the cross-linked hylan structure to hydroxyl radicals compared with the uncross-linked hyaluronan. (Al-Assaf et al. Radiat. Phys.Chem. 1995, Vol 46, 207-217); Identification of radicals from hyaluronan (hyaluronic acid) and cross-linked derivatives using electron paramagnetic resonance spectroscopy. (Al-Assaf et al. Carbohydrate Polymers, 1999, Vol.38, 17-22); The role of the proteinaceous component on the emulsifying properties of gum arabic. (Randall et al. Food Hydrocolloids, 1988, 2, No.2, 131-140); Structural and chemical properties of gum arabic. Their practical impact. (Phillips et al. Proceedings Gum Arabic Symposium, ZDS, Solingen, Germany, Jun. 6-8, 1988); The influence of structure and technology on gum arabic functionality. (Phillips, G., Supplement to Food Review February/March, 1988, pp.64-68); Fractionation and characterization of gum from Acacia senegal. (Randall et al. Food Hydrocolloids, 1989, Vol.3, No.1, p.65-75); The molecular characterization of the polysaccharide gum from Acacia senegal. (Osman et al. Carbohydrate Research, 1993, 246, pp. 303); The Classification of Natural Gums. Part III. Acacia senegal and Related Species (Gum Arabic); (Jurasek et al. Food Hydrocolloids, 1993, Vol.7, No.3, pp. 255-280); Acacia gum (Gum Arabic): a nutritional fibre; metabolism and calorific value. (Phillips, G., Food Additives and Contaminants, 1998, Vol. 15 No.3, 251-264); and, A review of recent developments on the regulatory, structural and functional aspects of gum arabic. (Islam et al. Food Hydrocolloids, 1997, Vol 11 (4), pp 357-365). Fractionation and characterization of gum from Acacia Senegal. (Randall et al. Food Hydrocolloids, 1989, Vol.3, pp.65-75) The molecular characterization of the polysaccharide gum from Acacia senegal. (Osman et al. Carbohydrate Research, 1993, 246, pp. 303); The Classification of Natural Gums. Part III. Acacia Senegal and Related Species (Gum Arabic) (Jurasek et al. Food Hydrocolloids, 1993, Vol.7, No.3, pp. 255-280).